Phase 1, Single Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MEDI5884

A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of MEDI5884 in Healthy Volunteers

A Phase 1, single dose study with 4 cohorts of ascending doses and an optional Japanese cohort designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of MEDI5884 in healthy volunteers

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: MEDI5884 Dose 1; Biological: Placebo; Biological: MEDI5884 Dose 2; Biological: MEDI5884 Dose 3; Biological: MEDI5884 Dose 4

Detailed Description

This is a first time in human, phase 1, randomized, blinded, placebo-controlled study to evaluate the safety, pharmacokinetics and pharmacodynamics of single ascending subcutaneous doses of MEDI5884 in healthy volunteers (age 18-55). The study consists of 4 cohorts of increasing doses (8 subjects each) and an optional Japanese American cohort (24 subjects) for a total of 56 healthy subjects. The decision whether or not to dose escalate will be based upon data review by the Dose Escalation Committee. Subjects will be randomized 3:1 to MEDI5884 or placebo. Following screening, the study consists of a 3 day inpatient stay and follow up visits. The number of follow up visits depend on the cohort assigned.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers aged 18-55 years
• Must provide written informed consent
• Ability and willingness to adhere to the protocol
• BMI 18-30kg/m2
• Females not of childbearing potential
• Males must practice 2 effective contraceptive measures if sexually active
• Japanese descent for the Japanese cohort

Exclusion Criteria:

• Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
• History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• Abnormal lab values, physical exam, vital signs
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing
• Positive Hepatitis B, Hepatitis C or HIV test
• Receipt of investigational therapy with 4 months from screening
• Current or previous use of systemic corticosteroids 60 days prior to dosing or lipid lowering medications 28 days prior to dosing
• Abnormal ECG
• Recent plasma or blood donation
• Positive drug or alcohol screen.
• Current smoker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI5884 Dose 1; Participants will receive single dose of MEDI5884 Dose 1 injection SC on Day 1.	Biological: MEDI5884 Dose 1; Participants will receive single dose MEDI5884 Dose 1 injection SC on Day 1.
Placebo Comparator: Placebo; Placebo will be administered subcutaneously (SC).	Biological: Placebo; Participants will receive single dose of placebo matched MEDI5884 injection SC on Day 1
Experimental: MEDI5884 Dose 2; Participants will receive single dose of MEDI5884 Dose 2 injection SC on Day 1.	Biological: MEDI5884 Dose 2; Participants will receive single dose MEDI5884 Dose 2 injection SC on Day 1
Experimental: MEDI5884 Dose 3; Participants will receive single dose of MEDI5884 Dose 3 injection SC on Day 1.	Biological: MEDI5884 Dose 3; Participants will receive single dose MEDI5884 Dose 3 injection SC on Day 1
Experimental: MEDI5884 Dose 4; Participants will receive single dose of MEDI5884 Dose 4 injection SC on Day 1.	Biological: MEDI5884 Dose 4; Participants will receive single dose MEDI5884 Dose 4 injection SC on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884	Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)	Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884	12 lead electrocardiogram (ECG) including RR (The time between corresponding points on 2 consecutive R waves on ECG), PR (ECG interval measured from the onset of the P wave to the onset of the QRS complex) , QRS (ECG interval measured from the onset of the QRS complex to the J point) , QT (ECG interval measured from the onset of the QRS complex to the end of the T wave), and QTc (QT interval corrected for heart rate) intervals	Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884	Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory rates)	Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884	Clinical laboratory assessments (serum chemistry, hematology, and urinalysis)	Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
HDL-Cholesterol over time	HDL-Cholesterol over time	Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipoprotein particle size	Lipoprotein particle size	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
Lipoprotein particle number	Lipoprotein particle number	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
Levels of total cholesterol	Levels of total cholesterol	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
Non-HDL-Cholesterol	Non-HDL-Cholesterol	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
Low-density lipoprotein cholesterol (direct and Friedewald equation)	Low-density lipoprotein cholesterol (direct and Friedewald equation)	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
Very low-density lipoprotein cholesterol	Very low-density lipoprotein cholesterol	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
Triglycerides	Triglycerides	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
Apolipoprotein B	Apolipoprotein B	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
Apolipoprotein A1	Apolipoprotein A1	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
MEDI5884 serum concentration: maximum observed concentration	MEDI5884 serum concentration: maximum observed concentration	Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4)
MEDI5884 serum concentration: time to maximum observed concentration	MEDI5884 serum concentration: time to maximum observed concentration	Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4)
MEDI5884 serum concentration: area under the concentration time curve	MEDI5884 serum concentration: area under the concentration time curve	Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4)
MEDI5884 serum concentration: terminal half-life	MEDI5884 serum concentration: terminal half-life	Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4)
Anti-drug antibody	Anti-drug antibody	Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2017
• Primary Completion (Actual): August 10, 2018
• Study Completion (Actual): August 10, 2018

Study Registration Dates

• First Submitted: November 23, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (Estimate): December 23, 2016

Study Record Updates

• Last Update Posted (Actual): August 22, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: atherosclerosis; acute coronary syndrome; MEDI5884
• Other Study ID Numbers: D7870C00001